The manufacture of bulk pharmaceuticals such as antibiotics is a competitive high-volume, low-profit enterprise, and co-product recovery is one method for increasing the profitability of this process. Many large scale pharmaceutical manufacturers use soybean meal to support the growth and secondary metabolite production of their fermentation microorganisms. For example, soybean meal is a common medium component of many pharmaceutical fermentations, including the erythromycin fermentation. Soybean flour contains isoflavones, which are valuable nutraceutical compounds. Leguminous plants such as soybean are also a rich source of isoflavones, a group of valuable compounds that can confer a variety of health benefits when consumed (Kaufman et al., Journal of Alternative and Complementary Medicine, 3(1):7-12, 1997). Legumes typically contain isoflavone glucosides as well as the isoflavones daidzein and/or genistein. It is the aglycone forms of isoflavones such as daidzein or genistein, referred to here as isoflavones, that are the primary biologically active compounds that confer health benefits when consumed. Purified isoflavones can also be used as intermediates in the synthesis of potential derivatives that can be used as drugs. At present purified genistein can cost up to about $2,370 a gram. Thus, a cost-effective isoflavone co-product recovery method would benefit soybean-based fermentation operations.
A previous study investigating isoflavone recovery focused on recovery of isoflavones from spent fermentation broth (U.S. patent application Ser. No. 11/464,700). In the study, it was found that isoflavones were not destroyed during the fermentation as originally thought (Hessler et al., Appl. Microbiol Biotechnol, 47:398-404,1997), but were converted into biotransformation products during the fermentation. Thus, this approach offered the first practical isoflavone recovery method for industrial soybean-based fermentations. However, several problems made this isoflavone co-product recovery approach less than ideal. One problem was that isoflavone biotransformation products must be converted back into their aglycone counterparts by acid hydrolysis in order to recover the desired form of the isoflavones. Another problem was that the isoflavone extract from treated spent fermentation broth would likely contain a wide array of contaminating compounds. Contaminants reduce the quality and marketability of the product unless the isoflavones are more highly purified, thereby introducing additional time and expense into the recovery process. The market for the highly purified crystalline isoflavones, however, is smaller than the market for more simply obtained concentrated isoflavone extracts.
It has been reported that the genistein in soybean flour might be responsible for the induction of desirable cytochrome P-450 enzymes of Streptomyces griseus during fermentation of that organism (Sariaslani and Kunz, Biochem Biophys Res Commun. 141(2):405, 1986.).
U.S. Pat. Nos. 5,320,949, 5,352,384, 5,637,561, and 5,637,562, each of which are incorporated herein by reference in their entireties, disclose methods for preparing isoflavone aglycone enriched soybean products.
Canadian Patent 02240795 discloses vegetable protein compositions containing an isoflavone depleted vegetable protein material with an isoflavone containing material dispersed therein and processes for producing the compositions.
Because of the widespread use of isoflavone-rich soybean-based fermentation media in the high-volume, low-profit manufacture of bulk pharmaceuticals, isoflavone co-product recovery is important for increasing the profitability of this process. Accordingly, a need still exists for soybean-based fermentation media that will support microorganism fermentation following co-product recovery.